POS0622 ASSOCIATION OF DIURNAL FLUCTUATION OF THE SOLUBLE TOLL-LIKE RECEPTORS 2 (sTLR2) WITH COMORBIDITY AND QUALITY OF LIFE IN WOMEN WITH RHEUMATOID ARTHRITIS
Authors: K. Zaichko, N. Zaichko
Journal: Annals of the Rheumatic Diseases (2022)

Background Disorders of circadian rhythms in the production of inflammatory mediators play an important role in the pathogenesis of rheumatoid arthritis (RA) [1]. Innate immune factors, in particular toll-like receptors 2 (TLR2), are involved in the formation of the inflammatory pattern in RA. Recently was shown that TLR2 play an important role in the development of atherosclerosis and hypertension [2]. Chronobiological aspects of innate immunity, in particular circadian rhythms of the soluble form of TLR2 (sTLR2) in RA and its comorbidity, requires further study. Objectives The aim of the study was to assess the daily variability of sTLR2 in RA patients depending on comorbid conditions and quality of life indexes. Methods In the study were enrolled 173 females with RA aged 45.9 (8.79) years and disease duration 7.96 (6.38) years. High activity of the RA (DAS28-ESR &gt; 5.1) were registered in 114 (66%) cases, moderate activity (DAS-28 3.2-5.1) - in 59 (34%) cases. 144 (83%) patients were seropositive by anticyclic citrullinated peptide (ACCP). Among enrolled subjects 140 (81%) had ІІ-ІІІ radiographic stage. There were 89 (51%) patients with comorbid pathology, including arterial hypertension (AH) - 59 (34%). Serum sTLR2 level was determined at 8:00 and 20:00 using Cloud-Clone Corp kits (USA). All stages of the study were carried out in compliance with bioethical standards and provisions of the WHO, Helsinki Declaration of the General Assembly of the World Medical Association (1989), Bioethical protocol No 1, 01 November 2016. *Data are mean (SD) or n (%). Results In patients with RA, daily fluctuations in sTLR2 levels were detected: indexes at 8:00 at 20:00 were lower than at 8:00 (343 (93.7) vs 272 (99.2) ng/L, р&lt;0.001). The mean difference between sTLR2 levels at 8:00 and 20:00 was -21.6 (13.2) %. In RA patients with AH, the average daily level of sTLR2 was higher (in 1.42 times, p &lt;0.001) than in RA patients without AH. Differences between RA with AH and RA without AH groups were more significant in the evening sTLR2 level (320 (112) vs 246 (81.3) ng/L, р&lt;0.01), than in the morning (378 (90.6) vs 321 (89.0) ng/L, р&lt;0.05). In the group RA with AH decrease in sTLR2 in the evening was less than in the group RA without AH (1.36 times, p &lt;0.05). An increase in sTLR2 at 20:00 was associated with a deterioration in mental health according to SF-36 (VT, SF, MH) in 1.2-1.3 times (highest quartile vs lowest quartile, р&lt;0.01). An increase in sTLR2 at 8:00 was associated with a decrease in physical health PF, RP, BP and GH (in 1.3-1.6 times, р&lt;0.01). Patients with high levels of sTLR2 showed more severe pain, impaired function, fatigue and sleep, decreased physical and emotional comfort, and control of symptoms according to RAID (in 1.3-1.4 times, р&lt;0.01). Conclusion In RA patients daily fluctuations in sTLR2 levels has been registered with the decrease of this index in the evening. In the case of comorbid AH production of sTLR2 is higher, especially in the evening time. Disorders of sTLR2 production are one of the factors that deteriorate the quality of life in patients with RA. References [1]Cutolo M. (2016) Glucocorticoids and chronotherapy in rheumatoid arthritis. RMD Open , 2:e000203. doi:10.1136/rmdopen-2015-000203 [2]Lazaridis A., Gavriilaki E., Douma S., &amp; Gkaliagkousi E. (2021) Toll-like receptors in the pathogenesis of essential hypertension. a forthcoming immune-driven theory in full effect. Int J Mol Sci, 22(7):3451. doi: 10.3390/ijms22073451. Disclosure of Interests None declared